Article
Biochemistry & Molecular Biology
Giovanna Gentile, Ottavia De Luca, Antonio Del Casale, Gerardo Salerno, Maurizio Simmaco, Marina Borro
Summary: Improper drug prescription is a major problem leading to drug-related harms and healthcare resource wastage. Through genomic profiling, we found that only 14.8% of Italian subjects had a fully normal cytochrome profile, while 26.5% had combined cytochrome dysfunction. The discussion focuses on the potential benefits of comprehensive pharmacogenomic testing in polytreated patients to improve drug selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Niels Westergaard, Lise Tarnow, Charlotte Vermehren
Summary: This study found that diabetic patients have significantly higher usage of antithrombotic agents and cardiovascular drugs compared to the general population, while the increase in analgesics, psycholeptics, and psychoanaleptics was relatively lower. The findings suggest that a large portion of diabetic patients are exposed to drugs with PGx-based dosing guidelines, supporting the idea of incorporating PGx-based decision-making into clinical practice.
Review
Chemistry, Medicinal
Jie Li, Shuting Wang, Fengjie Tian, Shuang-Qing Zhang, Hongtao Jin
Summary: As the use of herbs increases worldwide, there are more reports of interactions between herbs and drugs. The complex active components of herbs inevitably affect the pharmacokinetics of chemical drugs in vivo. The expression of drug transporters is closely related to the absorption, distribution, metabolism, and excretion of drugs. When herbs inhibit or induce the expression of transporters, it can result in changes in substrate pharmacokinetics, affecting the efficacy and toxicity of drugs. This article summarizes the tissue distribution and physiological functions of drug transporters, analyzes the effects of herbs on drug transporters, and discusses the possible mechanisms of herb-drug interactions, providing ideas and references for safe clinical drug use.
Article
Pharmacology & Pharmacy
Ruhul Kayesh, Vishakha Tambe, Chao Xu, Wei Yue
Summary: Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug-drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs. This study aimed to assess the OATP1B1- and OATP1B3-mediated DDI potential of the calcium channel blocker nicardipine. The results showed that nicardipine has the potential to cause OATP1B1/3-mediated DDIs, and the consideration of optimal preincubation conditions is important when assessing these interactions in vitro.
Article
Microbiology
Shawn Flanagan, Helen Walker, Voon Ong, Taylor Sandison
Summary: Rezafungin, a newly approved once-weekly echinocandin, has been shown to be free of severe drug-drug interactions (DDIs) according to extensive testing, making it a potential treatment for Candida infections and prevention of various infections.
MICROBIOLOGY SPECTRUM
(2023)
Article
Anesthesiology
Catherine Chanfreau-Coffinier, Sony Tuteja, Leland E. Hull, Sally MacDonald, Olga Efimova, Jill Bates, Deepak Voora, David W. Oslin, Scott L. DuVall, Julie A. Lynch
Summary: The response to analgesic therapy is influenced by various factors, including genetics and drug interactions. This study aimed to evaluate the potential impact of pharmacogenetic (PGx) testing on the care of Veterans with noncancer pain who were prescribed opioids metabolized by the CYP2D6 gene. The results showed that a significant proportion of patients were at an elevated risk for undesirable responses to their opioid medication based on predicted phenotypes and drug-drug interactions. However, CYP2D6 testing was infrequently used, and the results were mainly utilized to optimize antidepressant treatments rather than pain medications. The findings suggest that utilizing PGx testing along with consideration of phenoconversion may enhance the precision medicine approach to pain management in Veterans.
Article
Pharmacology & Pharmacy
Kyeong-Ryoon Lee, Ji-Eun Chang, Jongmin Yoon, Hyojeong Jin, Yoon-Jee Chae
Summary: Understanding the necessity of labeling for drug interactions based on in vitro findings is important. This study analyzed the in vitro findings and follow-up actions for drugs approved by the FDA's Center for Drug Evaluation and Research in the last five years. It was found that a certain percentage of drugs showed higher interaction values in in vitro studies, and some of them were labeled with potential drug interactions with supporting studies or scientific rationales. Other drugs were not labeled for interactions based on clinical studies or scientific rationales. This systematic and comprehensive analysis provides insights into the management of in vitro findings for transporter substrate or inhibitor drugs.
Article
Plant Sciences
Yajuan Bi, Xue Wang, Hui Ding, Feng He, Lifeng Han, Youcai Zhang
Summary: This review article summarizes recent progress in the research of natural product-drug interactions (NDIs), focusing on the main drug transporters and their interactions with natural products. The challenges and strategies of studying NDIs are also discussed.
Article
Pharmacology & Pharmacy
Alexander V. Dmitriev, Anastassia V. Rudik, Dmitry A. Karasev, Pavel V. Pogodin, Alexey A. Lagunin, Dmitry A. Filimonov, Vladimir V. Poroikov
Summary: This study aimed to create a computer model for predicting drug-drug interactions mediated by seven important P450 cytochromes. Using 2500 records as a training set, structure-activity relationship models were developed using PASS software and PoSMNA descriptors to predict metabolism-mediated DDIs between molecules. The average accuracy of the predictions was around 0.92, and the SAR models are publicly available for predicting DDIs mediated by the most important cytochrome P450 enzymes.
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena V. Grinkova, Mark A. McLean, Tyler Camp, Stephen G. Sligar
Summary: Human cytochrome P450 CYP3A4 plays a significant role in the metabolism of more than 35% of pharmaceuticals, leading to drug-drug interactions. This study evaluated the use of midazolam as a probe substrate to detect and predict the involvement of new drug candidates in CYP3A4-mediated drug-drug interactions. The results suggest that the changes in the shape and volume of the substrate-binding pocket explain the occurrence of drug interactions.
Article
Microbiology
Irene Hernandez-Lozano, Severin Mairinger, Thomas Filip, Mathilde Loebsch, Johann Stanek, Claudia Kuntner, Martin Bauer, Markus Zeitlinger, Marcus Hacker, Thomas H. Helbich, Thomas Wanek, Oliver Langer
Summary: Transporter-mediated drug-drug interactions (DDIs) can have serious safety consequences in antimicrobial drug development. This study used PET imaging-based PK analysis to evaluate the effect of different drugs on the tissue distribution and excretion of [F-18]ciprofloxacin as a model drug. Results showed that pretreatment with probenecid and cimetidine significantly decreased the renal clearance of [F-18]ciprofloxacin. The study highlights the importance of PET imaging-based PK analysis in assessing transporter-mediated DDIs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Hanqing Chen, Shuang Zhou, Meilin Zhu, Bing Wang, Wei Chen, Lingna Zheng, Meng Wang, Weiyue Feng
Summary: The study reveals that PEI-GNPs have significant effects on hepatic drug-metabolic enzymes and de novo lipogenesis in mice, leading to liver inflammation and partial hepatotoxicity. Therefore, it is crucial to consider the interaction between nanomaterials and the liver and modify the surface chemistry of GNPs before biomedical application.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Aishwarya Jala, Srikanth Ponneganti, Devi Swetha Vishnubhatla, Gayathri Bhuvanam, Prithvi Raju Mekala, Bincy Varghese, Pullapanthula Radhakrishnanand, Ramu Adela, Upadhyayula Suryanarayana Murty, Roshan M. Borkar
Summary: Transporter-mediated drug-drug interactions play a critical role in altering the pharmacokinetic profile of drugs, potentially impacting therapeutic efficacy and safety. Evidence suggests that many drugs can modulate the activity and expression of transporter proteins, emphasizing the importance of evaluating drug interactions during the drug development process.
DRUG METABOLISM REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Aleksi Tornio, Anne M. Filppula, Janne T. Backman
Summary: Multimorbidity, polypharmacotherapy, and drug interactions are prevalent in the ageing population. Drug-drug interactions can have negative health impacts, requiring translational research approaches to fully characterize the mechanisms, clinical effects, and implications of CYP-mediated DDIs.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Y. Anne Pak, Maria M. M. Posada, James Bacon, Amanda Long, William Annes, Jennifer Witcher, Malcolm Mitchell, Rommel G. G. Tirona, Stephen D. D. Hall, Kathleen M. M. Hillgren
Summary: The objective of this work was to demonstrate that clinical OAT1-mediated drug-drug interactions (DDIs) can be predicted using physiologically based pharmacokinetic (PBPK) modeling. The study shows that by measuring the inhibitory potency (IC50) of OAT inhibitors and conducting clinical DDI studies, PBPK modeling can accurately predict the occurrence and clinical effects of DDIs.
PHARMACEUTICAL RESEARCH
(2023)